Efficacy of ruxolitinib in patients with chronic neutrophilic leukemia and atypical chronic myeloid leukemia

Kim Hien T. Dao, Jason Gotlib, Michael M.N. Deininger, Stephen T. Oh, Jorge E. Cortes, Robert H. Collins, Elliot F. Winton, Dana R. Parker, Hyunjung Lee, Anna Reister Schultz, Samantha Savage Stevens, Chase Brockett, Nan Subbiah, Richard D. Press, Philipp W. Raess, Michael Cascio, Jennifer Dunlap, Yiyi Chen, Catherine Degnin, Julia E. MaxsonCristina E. Tognon, Tara Macey, Brian J. Druker, Jeffrey W. Tyner

Research output: Contribution to journalArticlepeer-review

59 Scopus citations


PURPOSE Colony-stimulating factor-3 receptor (CSF3R)-T618I is a recurrent activating mutation in chronic neutrophilic leukemia (CNL) and to a lesser extent in atypical chronic myeloid leukemia (aCML) resulting in constitutive JAK-STAT signaling. We sought to evaluate safety and efficacy of the JAK1/2 inhibitor ruxolitinib in patients with CNL and aCML, irrespective of CSF3R mutation status. METHODS We conducted a phase II study of ruxolitinib in 44 patients (21 CNL and 23 aCML). The primary end point was overall hematologic response rate (ORR) by the end of 6 continuous 28-day cycles for the first 25 patients enrolled. We considered a response as either partial (PR) or complete response (CR). We expanded accrual to 44 patients to increase our ability to evaluate secondary end points, including grade $ 3 adverse events, spleen volume, symptom assessment, genetic correlates of response, and 2-year survival. RESULTS ORR was 32% for the first 25 enrolled patients (8 PR [7 CNL and 1 aCML]). In the larger cohort of 44 patients, 35% had a response (11 PR [9 CNL and 2 aCML] and 4 CR [CNL]), and 50% had oncogenic CSF3R mutations. The mean absolute allele burden reduction of CSF3R-T618I after 6 cycles was greatest in the CR group, compared with the PR and no response groups. The most common cause of death is due to disease progression. Grade $ 3 anemia and thrombocytopenia were observed in 34% and 14% of patients, respectively. No serious adverse events attributed to ruxolitinib were observed. CONCLUSION Ruxolitinib was well tolerated and demonstrated an estimated response rate of 32%. Patients with a diagnosis of CNL and/or harboring CSF3R-T618I were most likely to respond.

Original languageEnglish (US)
Pages (from-to)1006-1018
Number of pages13
JournalJournal of Clinical Oncology
Issue number10
StatePublished - Apr 1 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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